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1.
Discov Med ; 36(184): 992-1001, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798258

RESUMO

BACKGROUND: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. METHODS: The DNP rat model was established through a high-fat-glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. RESULTS: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL-induced spinal nerve injury and inhibit mitophagy. CONCLUSION: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL-induced neurotoxicity.


Assuntos
Neuropatias Diabéticas , Lidocaína , Mitofagia , Proteínas Quinases , Ratos Sprague-Dawley , Ubiquitina-Proteína Ligases , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Lidocaína/farmacologia , Ratos , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Mitofagia/efeitos dos fármacos , Masculino , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(3): 203-207, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30907340

RESUMO

OBJECTIVE: To investigate the level of IgG antibody to varicella in the healthy population aged 1-19 years in Harbin, China. METHODS: Random sampling was performed to select 1 203 healthy individuals aged 1-19 years in Harbin. According to age, they were divided into ≥1 years group (n=240), ≥4 years group (n=396), ≥7 years group (n=364) and 14-19 years group (n=203). Enzyme-linked immunosorbent assay was used to measure the concentration of varicella-zoster virus (VZV)-IgG antibody in serum, and a concentration of VZV-IgG antibody of ≥100 mIU/mL was considered positive, suggesting that the subject had the ability to resist VZV infection. RESULTS: The overall positive rate of VZV-IgG antibody was 71.49% (860/1 203), and the concentration of VZV-IgG antibody was 447±17 mIU/mL. The concentration of VZV-IgG antibody tended to increase with age (P<0.05). The positive rate of VZV-IgG antibody in the urban population was significantly higher than that in the rural population (P<0.05). There was significant difference in the positive rate of VZV-IgG antibody between the populations with different doses of varicella vaccination (P<0.05), and the population with 2 doses of vaccination had the highest positive rate of VZV-IgG antibody. There was a significant difference in the concentration of VZV-IgG antibody between the populations with different medical histories (P<0.05), and the population with a past history of varicella had the highest concentration. CONCLUSIONS: Among the healthy population aged 1-19 years in Harbin, there is a significant difference in the level of VZV-IgG antibody between the urban and rural populations, as well as between different age groups. Varicella vaccination should be strengthened in areas with a low vaccination rate and the population aged <14 years.


Assuntos
Varicela , Adolescente , Adulto , Anticorpos Antivirais , Varicela/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Herpesvirus Humano 3 , Humanos , Imunoglobulina G , Lactente , Estudos Soroepidemiológicos , Adulto Jovem
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